Epidemiological survey of biomarkers of hepatitis virus in patients with extrahepatic cholangiocarcinomas

Aim: Hepatitis virus B and C (HBV and HCV) are suggested to be risk factors for intrahepatic cholangiocarcinoma (ICC), but whether they are risk factors for extrahepatic cholangiocarcinoma (ECC) is disputed. To test the biomarkers in patients with ECC and further elucidate the relationship of HBV or HCV infection with ECC risk, we conducted a retrospective survey on hepatitis virus markers in patients with ECC. Methods: A hospital-based case-control study was conducted to review prior infection with hepatitis virus and the seroprevalence of hepatitis virus markers in the patients with ECC or with benign biliary disease (BBD). HBV X antigen (HBxAg) was detected in the tissues by immunohistochemical staining. Results: A total of 305 patients with ECC and 480 with BBD were enrolled in this study. Compared with BBD patients, ECC patients had a higher prevalence of prior infection with HBV (6.2 vs 2.3%) and chronic HBV infection (9 vs 1.9%). The overall seropositive rate for HBV markers in the two groups was 22.6 versus 6% (P < 0.01) and for HBxAg detection it was 75 versus 26% (P < 0.001). The seroprevalence of anti-HCV was 4.3% in the EEC patients and 5.6% in BBD patients with no significant difference between them. Conclusion: The high prevalence of HBV biomarkers in ECC strongly supports the notion that HBV infection may be a risk factor for ECC. The high frequency of HBxAg expression suggests its important role in the pathogenesis of bile duct neoplasm.